Monday, September 13, 2010

Pediatrics study finds no link between thimerosal exposure via vaccines and autism

"This study revealed no increased risk of ASD associated with receipt of thimerosal-containing vaccines. No increased risk was found for subtypes of ASD, including ASD with regression, and prenatal exposure was not associated with a risk of ASD."

This latest study, available via open access, is published in Pediatrics. It's a much-anticipated, CDC-funded study that ought to put the lid once and for all on the vaccine-autism scare. No, I don't think that's really going to happen, but certainly, the results will soothe some fears.

As for those results, it's really pretty much as straightforward as the opening quote implies. This study was a case control, meaning that they matched children with ASD (n =256) and children without (n = 752) based on various demographic characteristics, including age, sex, and birth year. The children were born between 1994 and 1999. The authors determined thimerosal exposures by examination of patient charts and electronic registries and by performing parent interviews so that there isn't a whole lot of question about what exposures each child received. The case-control design helps to remove a number of potential confounding variables, while the reliance on charts for vaccine information provides a solid foundation for a pretty accurate measure of thimerosal exposure.

Further, they looked at separate categories of autism disorder: (1) autism spectrum disorder; (2) a category they term "autistic disorder"; and (3) the type that involved reported regression, termed "ASD with regression." In addition, they evaluated prenatal exposure as well as exposure from birth through 20 months.

In other words, this was a pretty comprehensive study design. Didn't involve rats or mice. Involved a thousand children. On-target with stating the hypothesis and relying on a study design that addresses that hypothesis as directly as possible. To determine whether or not a relationship exists between autism of any type and thimerosal exposure, they performed logistic regression analysis covering several overlapping time frames.

Their results are clear. Odds ratios were frankly in no way indicative of a relationship between thimerosal exposure up to age 20 months and the presence of ASD of any kind.

Of course, these numbers and these findings will do little to assuage anti-vax true believers. I have taken a stab at looking at this paper from the perspective of someone who believes in a big pharma-CDC conspiracy. From that perspective, here a few points I'd anticipate such a person would make:

First, there's the conflict of interest (COI). There's a financial disclosure statement in the paper (of course) in which these potential COIs are given:

Dr Marcy received honoraria for speaking for Merck and GlaxoSmithKline within the last 5 yearsGlaxoSmithKline within the last 5 years and grant support for studies on Gardasil and ProQuad from Merck within the last 5 years; Mr Lewis received grant support from Medimmune, Sanofi Pasteur, Chiron, Wyeth, Merck, and GlaxoSmithKline; and Dr Bernal received research funding from the CDC, the National Institute of Mental Health, Health Resources and Service Administration, and Autism Speaks. The other authors have no financial relationships relevant to this article to disclose.

Clearly, Big Pharma names are plastered all over this, as are the names of the other "conspirators," NIMH, the CDC, et al. Autism Speaks, which continues to mislead about a vaccine-autism link on its Website, is also listed here, and I'm not entirely sure how they'd fit into such a conspiracy.

So, of the 14 authors on this paper, three have financial disclosures to make, and none of these three is a lead or senior author on the paper. Not feeling a huge conspiracy here, but that's difficult for me anyway.

Then, I checked some of the data. Table 2 shows the average mercury exposures for the controls and the ASD children. They are all quite close in value with the exception of prenatal exposures in the ASD with regression group. (As an aside, I note that these values do not come close to the alleged "relevant" exposures used in the questionable Majewska rat study. Even the highest cumulative dose--accumulated over the course of 20 months--does not approach what they cumulatively gave the rats in the lowest-dose group in that study).

Table 3 shows the ORs derived from their analyses. Odds ratios show how much the odds might be decreased or increased with a given interaction of variables. An OR of around 1 means no difference in odds between the groups. Indeed, in Table 3, few ORs exceed 1 and none of them significantly, while several of them are well below one, indicating reduced odds. A companion technical paper is available to people who would like to examine all of the data and results in detail.

As the authors note:

In the covariate adjusted models, we found that an increase in ethylmercury exposure in 2 of the 4 exposure time periods evaluated was associated with decreased risk of each of the 3 ASD outcomes. We are not aware of a biological mechanism that would lead to this result. Analyses to explore potential explanations are presented in the technical re port.10,11 For example, there were no significant differences between case-children and controls in the numbers of vaccines received up to ages 7 or 20 months. Case-children were more likely to have received thimerosal-free or combined Hib vaccines than con- trols and more likely to have received thimerosal-free hepatitis B vaccines, resulting in the slightly lower cumulative exposure amounts.
This isn't the first time researchers have found a negative association between thimerosal exposure and autism.

Further, and this is interesting, they state in the discussion, "We found no evidence that the results were sensitive to extreme exposure amounts, extreme residual values, or were being driven by a few unusual individuals." They also performed an analysis to check for self-selection bias, given their low response rate, and found no indication of such a bias. Their use of charts as a double-check of parental recall also reduced the chances of squirrelly exposure data. I'm not seeing a conspiracy here, although I'm trying to find one.

Another thing alone that would militate against a conspiracy here is the lengthy acknowledgments section. There are dozens of people listed who were involved in several aspects of this work, from different representative organizations. Further, the cases came from three separate managed care organizations, which would be expected to help smooth any glaring single-source differences.

Finally, I note the description of how the study protocol was developed, which seems to have been done with even more than usual care, probably in anticipation of various negative responses:

"The study protocol was developed before data collection in consultation with a panel of external consultants that included autism advocates and experts in autism, child development, toxicology, epidemiology, biostatistics, and vaccine safety. All subgroup analyses and interaction tests were specified in the study protocol before data collection." In other words, there was a large group effort here with more inclusion than I can ever recall having seen on such a study before. They specified how all of the analyses would be done before embarking on data collection and adhered to that protocol. This inclusive, open approach ought to be the final nail in the coffin of a conspiracy theory, the final decomposition of the dead horse, the...well, insert your own hackneyed metaphor here.

The authors end their discussion with the following conclusion:
"The results of our study ... do not support the hypothesis that ethylmercury exposure from TCIs (thimerosal-containing injections) administered prenatally or during infancy is related to increased risk of ASDs."

I know this isn't the end of the question in the minds of some people, but I hope and genuinely also believe that it will lay to rest for many people their concerns about vaccines and autism.